Two Nature Biotechnology studies reported January 2 that aim to tighten base‑editing safety and targeting. One group introduced CHANGE‑seq‑BE, a sensitive, genome‑wide assay to profile base‑editor off‑target activity without bias; the other used directed evolution plus 3′‑extended guide RNAs to reduce bystander edits and sharpen adenine base editor (ABE) specificity. The lead finding is procedural and technical: researchers can now more reliably detect rare off‑target events genome‑wide and have engineered ABEs with measurably fewer unintended edits. Both papers included validation in cell models and recommended orthogonal assays for clinical candidate selection. These advances address two core obstacles to therapeutic base editing—accurate off‑target surveillance and enzyme precision—and provide tools sponsors can deploy during IND‑enabling studies to lower regulatory risk.